5-5289469-A-C

Position:

• chr5-5289469-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139056.4(ADAMTS16):​c.2790-13799A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 152,166 control chromosomes in the GnomAD database, including 4,186 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (4186 hom., cov: 34)
• Consequence: ADAMTS16 NM_139056.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.411

Genes affected

ADAMTS16 (HGNC:17108): (ADAM metallopeptidase with thrombospondin type 1 motif 16) This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family. ADAMTS family members share several distinct protein modules, including a propeptide region, a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS) motif. Individual members of this family differ in the number of C-terminal TS motifs, and some have unique C-terminal domains. The encoded preproprotein is proteolytically processed to generate the mature protein, which may inhibit chondrosarcoma cell proliferation and migration. This gene may regulate blood pressure. [provided by RefSeq, May 2016]

LOC101929200 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAMTS16	NM_139056.4	c.2790-13799A>C		intron_variant		ENST00000274181.7
LOC101929200	XR_001742583.3	n.2050+3098T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMTS16	ENST00000274181.7	c.2790-13799A>C		intron_variant		2	NM_139056.4	P1
ADAMTS16	ENST00000433402.2	n.2790-13799A>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34041 AN: 152048 Hom.: 4181 Cov.: 34

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.216

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.224 AC: 34067 AN: 152166 Hom.: 4186 Cov.: 34 AF XY: 0.227 AC XY: 16866 AN XY: 74396

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.375

Gnomad4 ASJ AF: 0.203

Gnomad4 EAS AF: 0.258

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.200

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.219

Alfa AF: 0.104 Hom.: 147

Bravo AF: 0.239

Asia WGS AF: 0.238 AC: 827 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.7
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs13172105; hg19: chr5-5289582;